Certain substituted omega-hydrazino alkanoic acid amines



United States Patent Ofilice 3,113,946 Patented Dec. 10, 1963 3,113,946 CERTAIN SUBSTITUTED OMEGA-HYDRAZINO ALKANOIC ACID AMINES Barry M. Bloom, Lyme, Conn, and Robert E. Carnelian, Evansville, Ind., assignors to Chas. Pfizer & Co., Inc., New York, N.Y., a corporation of Delaware No Drawing. Continuation of application Ser. N

808,919, Apr. 27, 1959. This application June 1, 1961, Ser. No. 114,019

10 Claims. (Cl. 260-295) R1 A-NHNH Z O O N in which Z is an alkylene radical containing 1 to carbon atoms; R; is hydrogen or lower alkyl; R is selected from the group consisting of alkyl and alkenyl preferably containing up to 5 carbon atoms; cycloalkyl containing 3 to 6 carbon atoms, pyridyl, pyridylalkyl, furylalkyl and thienylalkyl in which the alkyl group is lower alkyl, and ringsubstit-uted derivatives thereof in which said ring-substituent is a lower alkyl group; aryl and aralkyl represented by the formula:

wherein X is hydrogen, lower alkyl or halogen; Y is hydrogen, lower alkyl, lower alkoxy, halogen, trifluoromethyl, cyano or alkanoyl containing 2 to 4 carbon atoms; and n is an integer from 0 to 4.

A is hydrogen or an acyl group of the formula RC-- H 0 wherein R is selected from the group consisting of and wherein D is selected from the group consisting of alkyl and alkenyl containing up to 20 carbon atoms; a and b are su'bstituents each selected from the group consisting of hydrogen, amino, loweralkylamino, hydroxy, lower alkoxy, mercapto, lower alkylmercapto, halogen and alkanoylamino, alkanoyloxy and alkanoylmercapto, in which the alkanoyl group contains 2 to 4 carbon atoms. E is selected from the group consisting of cycloalkyl containing 3 to 6 carbon atoms, pyridyl, furyl, thienyl, thiazolyl, oxazolyl, isoxazolyl and ring-substituted derivatives thereof in which said ring-substituent is a lower alkyl group; m.- is an integer from 0 to 4, and X, Y and n are as previously described.

Also included within the scope of this invention are the acid addition salts of the basic nitrogen compounds described.

The alkylene radicals of which Z is representative are derived from aliphatic groups containing two unoccupied valences which permit them to be further connected as indicated for Z in the structural formula. Such radicals may be straight or branched and contain from 1 to 4 carbon atoms in their principal chain, that is, in the carbon chain between the two unoccupied valences. The carbon content of the various hydrocarbon substituents described above represents preferred substituents. These are preferred since compounds containing them are readily preparable and economical. Of course, substituents of higher carbon content may be employed.

The various hydrocarbon radicals described may be further substituted by the various substituents previously mentioned. Further, the aryl and heterocyclic radicals may be replaced by the corresponding benz-type compounds, that is, those containing a fused benzene ring, such as naphthalene, benzofuran, benzothiophene and the like, with no appreciable advantage being realized. Particularly valuable are compounds of the formula:

1 RC ONHNHZC ON especially those in which R is an aralkyl group. Additionally, those compounds in which RC0 is derived from an amino acid possess desirable therapeutic properties.

The new compounds of this invention may be prepared by reaction of an amine of the formula, R (R )NH, in which R and R are as described above, with corresponding lower alkyl esters of the formula:

ANHNHZCOOR wherein R is alkyl preferably containing 1 to 3 carbon atoms and A and Z are as described above. lit is obvious that these compounds in which A is an acyl group (RCO) may also be prepared by the acylation of the compounds in which A is hydrogen. Although the reaction may be brought about by simply mixing the selected amine with the alkyl ester and allowing the mixture to stand at room temperature (about 20 C.) for from about l to about 3 days, it is generally preferred to heat the reaction mixture to a temperature of from about 60 to about 200 C. since shorter reaction time is realized in so doing. For example, when the reaction is carried out at about C., a reaction time of 2 to 4 hours is found to give excellent yield of product. Generally, an equal molar ratio of reactants is employed although slight molar excesses (up to 10%) of amine may be advantageously used in the present process. The use of a larger excess provides no appreciable advantage and is not preferred. After the reaction is complete, the cooled reaction mass is recrystallized from a suitable solvent, such as ethyl acetate, lower alkanols, for example, methanol, ethanol, propanol, etc., and the like.

The above mentioned alkyl esters which are used in the preparation of the instant therapeutic agents may be prepared by procedures known in the art. One such procedure involves two steps, the first, the formation of the hydrazone of a suitable carbonyl compound, and the second, the reduction of the hydrazone to the desired ester.

The first of these reactions is brought about by refluxing the carbonyl compound with the selected hydrazine in a lower alkanol, such as methanol, ethanol or propanol, or aromatic hydrocarbon such as benzene, toluene, etc. Excellent yields are obtained after heating for periods of from about 1 to 4 hours. Many of the products separate almost instantaneously or initiating reaction. After the reaction is complete, the hydrazone is obtained by cooling the reaction mixture and filtering. The prodnot may be further treated by standard procedures of recrystallization. The second step, viz. hydrogenation of the hydrazone, may be accomplished by reaction with hydrogen over a platinum oxide catalyst. The hydrogenation is conveniently effected at pressures slightly higher than atmospheric pressure, for example, 30 to 50 pounds of hydrogen gas per square inch. The use of higher pressures provides no appreciable advantage and is therefore, not preferred. The selected condensation product is dissolved in a lower alkanol and reacted with hydrogen gas over the above-described catalyst, employed at 1% to by weight of the substrate. The mixture is shaken in a standard shaker apparatus until the theoretical quantity of hydrogen gas is taken up. The desired product is then obtained by the usual procedures of filtration of catalyst and concentration of the filtrate. Alternatively, a hydrazinoalkanoic acid ester of hydrazinoalkanoamide may be acylated to form those compounds in which A is an acyl group employing standard procedures, such as a suitable acid chloride (RCOCl) in the presence of pyridine. Additional preparative methods are obvious to one skilled in the art. For ex ample, the selected hydrazine compound may be reacted with a' suitable amide, such as Rr (C2 50)ZCHCH2CON to form ANHN=CHCH2C ON\ followed by hydrogenation of the resulting hydrazone to obtain the desired product.

It has been surprisingly found that a class of the alkyl esters from the group represented by the formula RCONHNHZCOOR;

as well as the corresponding amides of the formula .RC ONHNHZC ON in which R R and R are as described above and R is hydrogen or lower alkyl containing 1 to 3 carbon atoms. This class of compounds is represented by the formula-RCONHNHCH(R )CH COG. Interfering groups such as amino, hydroxy and mercapto should not be present in the acylhydrazide, RCONHNI-I employed in this process. Such groups are known to react with O o-unsaturated acids and may appreciably reduce the yield of desired product. Those compounds in which R contains free mercapto, amino and hydroxy groups are best prepared by protecting these free groups, for example, by acylation. The reaction is best eifectedemploying acylhydrazides, RCONHNH in which R is E(CH in which E and m are as previously described;

in which X, Y and n are as previously described;

in which D is as previously described and c and d are substituents each selected from the group consisting of hydrogen, lower alkylamino, halogen, lower alkoxy,

The reaction is carried out by heating a mixture of the two reactants in at least an equimolar ratio in an inert organic solvent and in the presence of a lower alkanoic acid which is generally employed in catalytic amounts. At least 1% of alkanoic acid by volume of the total reaction mixture should be employed. Generally, it is found that the optimum level of alkanoic acid is from 1% to 5% by volume of the total reaction mixture. Larger amounts of catalyst may be used but reduced yield of product may be realized in so doing. Although it is preferred to employ acetic acid as catalyst, other lower alkanoic acids may be used, viz. formic, propionic, butyric and the like. By inert organic solvents as employed herein is meant an organic solvent which dissolves the reactants but does not react with same under the reaction conditions described. Such solvents may be readily determined by routine experimentation in the laboratory. Although a number of other solvents may be employed, excellent results are obtained when using tertiary alcohols. alcohols in which there is no hydrogen on the carbon atom to which the hydroxy group is attached, each of the valences of this carbon atom are involved in carbon to carbon linkage. Exemplary of these alcohols are tertiary butyl alcohol, 1,1-dimethylpropanol, 1,1-dimethylbutanol, l-methyl-l ethylbutanol, l,1-dimethy1pentanol and the like. The mixture is conveniently heated at the reflux temperature of the solvent, although lower temperatures may also be employed, for example, a temperature of 50 C. The reaction is completed in as little as 6 hours although generally, time periods of from 6 to 18 hours at the above specified temperatures are employed. In many cases, the use of excess a,,8-unsat urated acid ester is found to appreciably improve the yield of the product. Up to 40% molar excess of unsaturated ester is found to' enhance the yield of product. After the reaction is complete, the product is obtained by standard procedures, such as concentration, crystallization and filtration procedures. The product may be purified by standard procedures of recrystallization from solvents such as lower alkanols for example, methanol, ethanol, propanol, etc., ethyl acetate, acetone and the like.

The new therapeutic agents of the present invention possess a considerably higher activity in the treatment of mental depression than prior art agents. Further, the instant agents possess a higher therapeutic index than prior art agents. Therapeutic index as employed herein refers to the ratio of therapeutic activity to toxicity. The

A use of many prior art agents in the treatment of mental depression is attended by considerable toxic reactions in the patient. The ratio of activity to toxicity of a therapeutic agent is obviously most important in selecting such an agent. Although many agents are quite active therapeutically, their use is seriously curtailed by exces sive toxicity. The present therapeutic agents, due to their high therapeutic index, are more desirable for treatment of mental depression than prior art agents. The new therapeutic agents of this invention in which R is a 4- pyridyl radical additionally possess appreciable antitubercular activity, while those in which R is phenyl, 2- pyridyl, 3-pyridyl, thienyl, or furyl radicals do not.

The physician will indicate daily dosage of the therapeutic agents of this invention. The dosage will be dependent upon the extent of mental depression, whether mild or severe. In cases of mild depression, dosage of from 10 to 50 milligrams per day may be indicated.

Tertiary alcohols, as is Well known, are

In severe depression, considerably higher daily dosage may be required, for example, up to 150 milligrams and higher. Tablets or capsules containing 10, 25, 50 and 150 milligrams of the instant therapeutic agents are convenient unit dosage forms for daily administration. Such tablets or capsules may be prepared from mixtures of the present compounds with Well known pharmaceutical excipients, such as starch, sugar, tapioca, certain forms of clay and the like. Alternatively, liquid preparations may be prepared from mixtures of the present therapeutic agents and pharmaceutically acceptable liquid media, such as Water, aqueous glycols, sugar solutions and the like which may contain conventional flavoring and coloring agents.

Since many of the compounds of the present invention are basic, advantage may be taken of the water solubility of salts of these compounds formed with acids in the isolation and/or purification of the above compounds and in the preparation of aqueous solutions of these new compounds for oral or parenteral administration. Of course, only salts formed with pharmaceutically-acceptable acids should be employed in therapeutic applications. Particularly effective salts are those formed with pharmaceutically-acceptable acids having a pK value of 3 or lower. Such acids are well-known in the art, for example, hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, benzenesulfonic, toluenesulfonic, methylsulfonic, ethylsultonic acids and the like. These salts may be prepared by procedures commonly employed in the art, for example, reacting the compound with an equivalent of the selected acid in aqueous solution and concentration of the solution. Other known procedures may also be employed.

The following examples are given by Way of illustration and are not to be construed as limitations of this invention many variations of which are possible within the scope and spirit thereof.

EXAMPLE I N-Benzyl-Beta-(Isonicotinylhydmzino)Propiomzmide A slurry of 7.5 g. (0.034 mole) of l-isonicotinyl-Z-(carbomethoxyethyD-hydrazine and 5 ml. of benzylamine is heated with stirring at 130 for three hours. The cooled mass is then recrystallized from ethyl acetate to yield White needles melting at l51.l-152.l C. Elemental analysis gives the following results:

Calcd. for C H N O: C, 64.43; H, 6.07; N, 18.77. Found: C, 64.43; H, 6.27; N, 19.17.

EXAMPLE II N-Benzyl-Beta-(Benzoylhydrazino)Propionamide This compound is prepared by the procedure of Example I employing l-benzoyl-Z-(carboethoxyethyl)hydrazine in place of the corresponding isonicotinyl compound. The product melts at 164-l65 C. Elemental analysis agrees with the calculated values.

EXAMPLE :III

N-(p.Chl0r0benzyZ) -(Beta-lsonicotinylhydrazino) Propz'onamide The procedure of Example I is repeated employing p.chlorobenzylamine in place of benzylamine. The product melts at 162l63 C.

EXAMPLE IV N-(4-Pic0lyl)Bela-(Benzoylhydrazino)Propionamide This compound is prepared by the procedure of Example I employing 4-picolylamine and l-benzoyl-Z-(carbomethoxyethyl)hydrazine. The product melts at 125 127 C.

Additional N-substituted-betaacylhydrazino) propionamides prepared employing suitable 1-acyl-2-(carboalkoxyethyl)hydrazines and appropriate amines are:

N benzyl beta-(Z-furoylhydrazino)propionamide (MD.

N furfuryl beta-(isonicotinyihydrazino)propionamide (M.P. 129-131 C.)

N phenylethyl beta (isonicotinylhydrazino)propionamide (M.P. 145-l47 C.)-

N (3,4-dimethoxyphenylethyl)-beta-(isonicotinylhydrazino) propionamide (M.P. -114 C.)

N-(3-methylbenzyl) beta (isonicotinylhydrazino)propionamide (M.P. 114-116 C.)

N (4 methylbenzyl) beta-(isonicotinylhydrazino)propionamide (M.P. 133-135 C.)

N-(2 chlorobenzyl) beta (isonicotinylhydrazino)propionamide (M.P. 148-149 C.)

N (2 methylbenzyl) beta-(isonicotinylhydrazino)propionamide (M.P. 148-149 C.)

N-(3,4 dichlorobenzyl) beta (isonicotinylhydrazino)- propionamide (M.P. 139-140 C.)

N (2,4 dichlorobenzyl) beta-(isonicotinylhydrazino)- propionamide (M.P. 137-139 C.)

N benzylbeta-(nicotinylhydrazino)propionamide (M.P.

N-benzyl-beta (cycloheXy-lcarbohydrazino)propionamide (M.P. 150-152" C.)

N methyl beta (isonicotinylhydrazino)propionamide (M.P. 119 C.)

N-ethyl-beta- (isonicotinylhydrazino propionamide (M.P.

N-n-propyl beta (isonicotinylhydrazino)propionamide (M.P. 118-120 C.)

N i propyl beta-(isonicotinylhydrazino)propionamide Ml. 163-165 C.)

N-n butyl beta (isonicotinylhydrazino)propionamide (M.P. 120-122 C.)

N i butyl beta (isonicotinylhydrazino)propionamide (M.P. 146-147 C.)

N-cyclohexyl-beta (isonicotinylhydrazino)propionamide (M.P. 166-167 C.)

N-allyl-beta-(isonicotinylhydrazino)propionamide (M.P.

N-phenethyl beta (isonicotinylhydrazino)propionamide (M.P. -147 C.)

N-benzyl-beta-(3 chlorobenzoylhydrazino)propionamide (M.P. 151-153" C.)

N benzyl beta-(4-fiuorobenzylhydrazino)propionamide (M.P. 214-216 C.)

EXAMPLE V N -Benzy l-oc-H yarazinoa'cemrmide This compound is prepared by the procedure of Example I employing benzylamine and methyl a-hydrazinoacetate.

Similarly, additional N-substituted hydrazinoalkanoamides are prepared employing suitable amines:

N-methyl-N-benzyl-a-hydrazinoacetarnide N-pyri dyl-a-hydrazinoacetamide N-n-propyl-a-hydrazinoacetamide N- (p-chlorobenzyl) -a-hydrazinoacetamide N- Z-furfuryl) -m-hydrazinoacetamide N-( allyl) -a-hydrazinoacetamide N-benzyl-B-hydrazinopropionamide N-allyl-B-hydrazinopropionamide N-n-propyl-E-hydrazinohexanoamide N-cycl obutyl-a-hydrazinoacetamide N-pentenyl-a-hydrazinopropionamide N-cyclohexyl-N-methyl-B-hydrazinobutyramide N-phenethyl-a-hydr azinobutyr amide N-4-chlorobenzyl-B-hydrazinopropionamide N-4-fiuorobenzyl-u-hydrazinopropionamide N-4-methylbenzyl-u-hydrazinopropionamide N-3,4-dichlorobenzyl-a-hydrazinopropionamide N-2,4-dibromobenzyl-1x-hydrazinopropionamide N-4-io dobenZyl-fi-hydrazinopropionamide N-3-methylbenzyl-fi-hydrazinopropionamide N-4-propylphenyl-fi-hydrazinopropion amide N-phenyl-fi-hydr azinopropionamide l-nicotinyl-2- e-carboethoxypentyl hydrazine -1-b enzoyl-2- fl-carboethoxybutyl hydrazine 1 -isonicotinyl-2- 'y-c arb opropoxypropyl) hydrazine 1-benzoyl-2- a-methyl, B-carbomethoxypropyl hydrazine 1-isonicotinyl-2- a-methyl, fl-carboethoxybutyl hydrazine l-benzoyl-Z- a-propyl, -fi-carboethoxyethyl hydrazine 1-isonicotinyl-2- fl-carb omethoxyethyl) hydrazine 1- (2-furoyl) 2- fi-carbomethoxyethyl) hydrazine 1-isonicotinyl-2- ,B-c arboethoxyethyl) hydrazine 1 (3 -furoyl) 2- (a-methyLfi-carboethoxypropyl hydrazine 1-benzoyl-2-(B-carbopropoxypropyl) hydrazine 1-picolinoyl-2- ,Bcarbomethoxybutyl hydrazine l- Z-thenoyl) -2- flcarbomethoxyethyl) hydrazine 1- (3 -thenoyl) -2- (ficarbomethoxyethyl hydrazine Other 1-acyl-2-(carbalkoxyalkyl)hydrazines employed in the previous examples are prepared employing this procedure.

EXAMPLE VIII Preparation Compounds of the Formula $3 RGONHNHCHOHzOOG These compounds are prepared by heating a selected acylhydrazine with an a,}9-unsaturated acid ester or amide with glacial acetic acid in an alkanol solvent.

For example, methyl acrylate, 28.0 g. (0.4 mole) was added dropwise during one hour to a solution containing 54.8 g. (0.4 mole) of isonicotinic acid hydrazide and 10 ml. of glacial acetic acid in 400 ml. of tertiary butyl alcohol. The resulting solution then was heated for 18 hours on a steam bath. Concentration of the reaction mixture to 100 ml. yielded 13.0 g. of unreacted isonicotinic acid hydrazide. The filtrate was concentrated to a thick syrup which was triturated with anhydrous ether and recrystallized from isopropyl alcohol; M.P. 8788.5 C. Elemental analysis of the product, 1-isonicotinyl-2-(ii-carbomethoxymethyl)hydrazine, gave the following results:

Calcd. for C H H O C, 53.81; N, 5.87. Found: C, 54.08; N, 5.65.

Employing this procedure, the following hydrazines are prepared from suitable n p-unsaturated acid derivatives as listed in Table III and corresponding acylhydrazines, in 1020% yields.

zme. 1-(8-thenoyD-2- (flcarbomethoxyethyl) hydrazine.

methyl acrylate.

Hydrazinc product l a (RC ONHNHOHCHZC ON :1, fl-unsaturated ester N-benzyl-fl- (benzoylhydrazino) proplonarm'de- N-phenethyl-fl-(picolinylhydrazino)butyramide. N-cycllohexyl-fi-(benzoylhydrazino) pentanoami e. N-methyl-N-benzyl-B-(benzoylhydrazino) propionamide.

N-allyl-fi-(isonicotinylhydrazino)hexanoamide.

N-n-propyl-fl-(Z-turoylhydrazino)propionamide N -bcr 1dzyl-fl- (isoxazolylcarbohydrazino)propionarm e.

N-benzylacrylamide.

N-(phenethyl) acrylamide.

N-cyclohexylpentenoami e. N-methyl-N-benzylacrylamide. N-allylhcxenoamide. N-n-propylacylamide. N-bcnzylaerylamide.

The hydrazines of the same general formulae mentioned in the previous examples are prepared in the same manner from corresponding o e-unsaturated acid derivatives and acylhydrazines.

. The reactions are carried out using as solvents tertiary alcohols such as tertiary butanol, 1,1-dimethylpropanol, 1,1-dimethylbutanol and l-methyl-l-ethylbutanol.

The starting materials for the above described reactions, viz. the carbonyl compounds and the c p-unsaturated esters, are readily available in most cases or easily preparable by conventional procedures well known in the art. The acid hydrazides employed are well-known compounds which are readily available or preparable by standard procedures from acids such as benzoic acid, 2-furoic acid, 3-furoic acid, 2-thenoic acid, pyridine-2-pyridine-3- and pyridine-4- carboxylic acids.

EXAMPLE IX The procedure of Example VIII is repeated employing a 40% molar excess of methyl acrylate. The yield of product is 40%.

EXAMPLE X A tablet base was prepared by blending the following ingredients in the proportion by weight indicated.

Sucrose, U.S.P. 80.3 Tapioca starch 13.2 Magnesium stearate 6.5

Into this base there was blended sufficient N-benzyl-betaisonicotinylhydrazinopropionamide to provide tablets each containing 10, 25, 50 and mg. of active ingredient.

Other therapeutic agents as exemplified in the above examples were similarly blended into this tablet base.

EXAMPLE XII Aqueous suspensions were prepared each containing 25 mg. per teaspoonful (5 ml.) of each of the above described therapeutic agents in avehicle composed of U.S.P. simple syrup containing the following materials per 100 ml. of vehicle.

RD. & C. Yellow No. 5 mg 5 Carboxymethylcellulose low-viscosity type mg 1 Synthetic lemon flavor (Freitsche) ml 0.5

These suspensions are partly cloudy but well adapted for oral administration of the active agent.

In addition to their use in the treatment of mental disease, the compounds of the present invention are effective monamine oxidase inhibitors especially in the central nervous system and are also useful for the relief of anginal pain. Many of these compounds possess anti-convulsant properties. These compounds are additionally useful for the amelioration of mood in rheumatoid arthritis, etc.

This application is a continuation of application Serial No. 808,919, filed April 27, 1959, now abandoned, which in turn is a division of application Serial No. 784,083, filed December 31, 1958 and now US, Letters Patent No. 2,894,972 of July 14, 1959, which in turn is a continuation-in-part of application Serial No. 749,061, filed July 17, 1958 and now abandoned.

13 What is claimed is: 1. A compound selected from the group consisting of compounds represented by the formula:

wherein Z is alkylene having 1 to 5 carbon atoms;

R is selected from the group consisting of hydrogen and lower alkyl;

R is selected from the group consisting of alkyl and alkenyl each having up to 5 carbon atoms; cycloalkyl having 3 to 6 carbon atoms; pyridyl, pyridylalkyl, furylalkyl and thienylalkyl in which the alkyl group is lower alkyl, and ring-substituted derivatives thereof in which each ring substituent is lower alkyl; and

wherein X and Y are as described above; and the acid addition salts thereof.

2. The compound of the formula:

wherein Z is alkylene having two carbon atoms in the principal chain and a total of up to carbon atoms, R is hydrogen, R is phenylalkyl having up to four carbon atoms in the alkyl moiety and R is furyl.

3. The compound of the formula:

wherein Z is alkylene having two carbon atoms in the principal chain and a total of up to 5 carbon atoms, R is hydrogen, R is phenylalkyl having up to four carbon atoms in the alkyl moiety and R is halophenyl having up to two halo substituents on the phenyl radical.

4. The compound of the formula:

wherein Z is alkylene having two carbon atoms in the principal chain and a total of up to 5 carbon atoms, R is hydrogen, R is phenylalkyl having up to four carbon atoms in the alkyl moiety and R is monosubstituted phenyl in which the substituent is lower alkoxy.

5. The compound of the formula:

ll 0 R2 wherein Z is alkylene having two carbon atoms in the principal chain and a total of up to 5 carbon atoms, R is hydrogen, R is phenylalkyl having up to .four carbon atoms in the alkyl moiety and R is isoxazolyl.

6. The compound of the formula:

wherein Z is alkylene having two carbon atoms in the principal chain and a total of up to 5 carbon atoms, R is hydrogen, R is phenylalkyl having up to four carbon atoms in the alkyl moiety and R is 3-pyridyl.

7. N-benzyl-B-(Z-furoylhydrazino)propionamide.

8. N benzyl ,8 (4 fluorobenzoylhydrazino)propionamide.

9. N-benzyl-B- (benzoylhydrazino propionamide.

10. N-benzyl-fl-(nicotinylhydrazino)propionamide.

References Cited in the file of this patent UNITED STATES PATENTS 2,723,273 Rogers Nov. 8, 1955 2,746,968 Hegediis May 22, 1956 2,808,414 Ward Oct. 1, 1957 2,855,402 Cramer Oct. 7, 1958 2,866,795 Swain Dec. 30, 1958 2,874,189 Micucci et al. Feb. 17, 1959 2,908,687 Ban Oct. 13, 1959 2,908,688 Gardner et a1. Oct. 13, 1959 2,939,539 Guttmann et al. Apr. 26, 1960 2,953,598 Clark et a1 Sept. 20, 1960 2,984,685 Holmen May 16, 1961 2,999,880 Wheatley et al Sept. 12, 1961 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF COMPOUNDS REPRESENTED BY THE FORMULA:
 6. THE COMPOUND OF THE FORMULA: 